4-87478958-A-G

Variant names:

• chr4-87478958-A-G
• rs4610302
• NM_004684.6:c.1966+472T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004684.6(SPARCL1):​c.1966+472T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.692 in 152,090 control chromosomes in the GnomAD database, including 37,516 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.69 (37516 hom., cov: 31)
• Consequence: SPARCL1 NM_004684.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0680
• Publications: 14 publications found

Genes affected

SPARCL1 (HGNC:11220): (SPARC like 1) Predicted to enable calcium ion binding activity; collagen binding activity; and extracellular matrix binding activity. Predicted to be involved in anatomical structure development and regulation of synapse organization. Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

SPARCL1 Gene-Disease associations (from GenCC):

• stromal corneal dystrophy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPARCL1	NM_004684.6	c.1966+472T>C		intron_variant	Intron 10 of 10	ENST00000282470.11	NP_004675.3
SPARCL1	NM_001128310.3	c.1966+472T>C		intron_variant	Intron 11 of 11		NP_001121782.1
SPARCL1	NM_001291976.2	c.1591+472T>C		intron_variant	Intron 11 of 11		NP_001278905.1
SPARCL1	NM_001291977.2	c.1591+472T>C		intron_variant	Intron 9 of 9		NP_001278906.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPARCL1	ENST00000282470.11	c.1966+472T>C		intron_variant	Intron 10 of 10	1	NM_004684.6	ENSP00000282470.6
SPARCL1	ENST00000418378.5	c.1966+472T>C		intron_variant	Intron 11 of 11	5		ENSP00000414856.1
SPARCL1	ENST00000503414.5	c.1591+472T>C		intron_variant	Intron 11 of 11	2		ENSP00000422903.1

Frequencies

GnomAD3 genomes AF: 0.692 AC: 105124 AN: 151972 Hom.: 37470 Cov.: 31

Gnomad AFR AF: 0.852

Gnomad AMI AF: 0.718

Gnomad AMR AF: 0.751

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.799

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.678

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.692 AC: 105223 AN: 152090 Hom.: 37516 Cov.: 31 AF XY: 0.694 AC XY: 51594 AN XY: 74344

African (AFR) AF: 0.852 AC: 35349 AN: 41508

American (AMR) AF: 0.751 AC: 11485 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 2378 AN: 3468

East Asian (EAS) AF: 0.632 AC: 3254 AN: 5146

South Asian (SAS) AF: 0.798 AC: 3842 AN: 4816

European-Finnish (FIN) AF: 0.566 AC: 5986 AN: 10580

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.598 AC: 40637 AN: 67966

Other (OTH) AF: 0.679 AC: 1433 AN: 2110

Alfa AF: 0.643 Hom.: 87510

Bravo AF: 0.708

Asia WGS AF: 0.747 AC: 2597 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.50
PhyloP100		-0.068
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4610302; hg19: chr4-88400110;